Conventional type 1 dendritic cells (cDC1) as cancer therapeutics: challenges and opportunities

The use of dendritic cell (DC)-based cancer vaccines over three decades has shown them to be a safe therapeutic approach against a range of hematological and solid malignancies. However, underwhelming and inconsistent results from clinical trials have seen them move in and out of favor. The limitations of ex vivo generated monocyte-derived DC (MoDC) in these therapies provide a pointed explanation for the varying and somewhat disappointing clinical outcomes. The identification of a specialized role for the rare conventional type 1 dendritic cell (cDC1) subset in orchestrating tumor immunity via the initiation of CD8⁺ T cell responses has led to a new concept of targeting cDC1 as a therapeutic option to address the unmet need of enhancing the immune response in cancer patients.

This article reviews several current challenges and key opportunities associated with the development and use of next generation cDC1 cancer vaccines.

Manipulation of cDC1 quantity and quality holds enormous potential to improve tumor immunogenicity, as already demonstrated in preclinical models. New technologies are rapidly advancing the understanding of cDC1 in human cancer patients and facilitating the generation of these extremely rare cells in vitro, providing feasible new approaches toward clinical translation.